Telomere is a part of DNA that exists at the end of chromosome. In the initial stage of a human chromosome gene that comprises repetitive sequences of TTAGGG, telomere is a DNA having a length of about 10 kb. Various types of proteins bind to telomere, which therefore acts to prevent the ends of DNAs from bonding to each other to form a cyclic DNA, or acts to bond to nuclear membranes. A majority of telomere is double-stranded, but several tens of bases at the outermost 3′-terminal end protrude as single-stranded.
In cell division, DNAs are replicated. In the replication mechanism, however, the replicated RNA primer moiety is not substituted with DNA in every replication, and therefore the 5′-terminal side telomere is shortened. At the same time, the 5′-terminal side including the parent DNA that has been the template for the replication is modified, and, as a result, the telomere moiety of both the parent DNA and the child DNA is shortened after the DNA replication. This was reported in 1972 in theory, and in 1989, it was clarified that the telomere moiety is shortened by about 50 to 150 bases or so in every DNA replication. When the length of the telomere moiety becomes about 5 kb or so, the cell division life thereof comes to an end (M1 stage) and no more cell division occurs. In normal cells, TRF1, a type of telomere-binding protein binds to the double-stranded (duplex) part of telomere, and it inhibits telomere extension. After having reached the end of cell division life thereof, the telomere DNA in the cells becomes gradually unstable, and at last it could not keep the chromosome stability to lead to apoptosis (M2 stage).
On the other hand, an enzyme “telomerase” having the ability to extend the sequence of telomere exists in cancer cells, in which the telomere chain having been shortened through cell division is prolonged by the enzyme. It is therefore said that cell growth may repeat endlessly in cancer cells. Because of this reason, it is believed that, different from normal cells, cancer cells abnormally repeat their growth not undergoing the above-mentioned M1 stage and M2 stage. Given that situation, it is expected that a compound capable of inhibiting the telomere chain extension to be effected by the telomerase peculiar to cancer cells could be a carcinostatic agent of the coming generation.
Telomerase is a reverse transcriptase having the ability to extend the single-stranded moiety of a telomere DNA, and contains inside it a complementary chain template RNA that corresponds to 1.5 times TTAGGG. Telomerase acts for chain extension based on the template RNA serving as a primer.
It is known that the telomere chain forms a quadraplex of four DNAS. It is believed that, when the quadraplex structure of the telomere chain could be stabilized, then the telomere chain extension to be caused by telomerase might be inhibited, and members of many study groups in the world are now studying the matter.
On the other hand, since telomerase after all extends the single-stranded part of telomere DNA as so mentioned hereinabove, we, the present inventors have had an inspiration that the telomerase activity might be inhibited if the single-stranded part of telomere DNA could be stabilized as a duplex structure such as a hairpin structure. This our inspiration is a novel technical idea, basically different from the above-mentioned quadraplex structure stabilization.
However, the complementary sequence necessary for forming the hairpin structure for the single-stranded telomere chain is TA only, and even if a complementary chain is formed for the part of “TA” as in the following, some base mismatches such as G-G mismatch will occur before and after the thus-formed complementary chain.

The above-mentioned sequence is to schematically show the 3′-terminal side single-stranded part of telomere that has formed a hairpin structure. Concretely, the right-hand side of the sequence is a loop moiety of the hairpin structure and is single-stranded as a whole. The 5′-side of the single-stranded telomere terminal is a duplex DNA, and the 3′-side thereof is the end of telomere, or that is, the end of chromosome. The vertical lines in the above-mentioned sequence mean that the indicated parts are complementary to each other, but the other parts are mismatches.
As in the above, it is generally difficult to form a stable hairpin structure in the single-stranded part of telomere, and in cancer cells, telomerase acts on the single-stranded part of telomere to thereby extend the telomere chain. However, if the base mismatches such as G-G mismatch could be solved in the single-stranded part of telomere, a stable hairpin structure could be formed in the single-stranded part of telomere and the telomerase activity on that part could be inhibited.
We, the present inventors have developed a bulge DNA recognition molecule that specifically binds to a DNA (bulge DNA) having an unpaired base (bulge base) to be formed in a duplex DNA to thereby stabilize it (Japanese Patent Application No. 11-262205). The bulge recognition molecule does not only bind to such an unpaired base through hydrogen bonding therebetween but also intercalates into the space formed by the presence of the bulge base, based on the stacking interaction between the aromatic ring of the molecule and the base around the bulge, and the molecule thereby stabilizes the bulge base.
We, the present inventors have further studied the action on the unpaired bases that is based on the stacking effect of the peripheral bases around them, and, as a result, have found that a compound having two different molecules each capable of forming a pair with a base can be relatively stably taken even in the site of base pair mismatches owing to the stacking effect as above, and have succeeded in providing a reagent capable of detecting and identifying the mismatched base sequences (Japanese Patent Application No. 11-336620).